.alpha.,.alpha.-Disubstituted amino acids are of great interest for a variety of reasons. They have been shown to be effective inhibitors of enzymes which normally metabolize the corresponding proteinogenic amino acids (Almond et al., Biochem., 1, 243 (1962); Pankaskie et al., J. Med. Chem., 23, 121 (1980)). The additional substituent of such amino acids can have a marked effect on the conformation of peptide structure, thus they can be utilized to modify physiologically important peptides to stabilize preferred conformations (Burgess, Proc. Natl. Acad. Sci. USA, 91, 2649 (1994)). They also occur as constituent parts of interesting natural products (Koert, Nachr. Chem. Tech. Lab., 43, 347 (1995)). As such any effective preparation of .alpha.,.alpha.-disubstituted amino acids, in an enantiocontrolled fashion, is highly desirable.
5(4H)-Oxazolones have been known for some time, and are prepared by the direct dehydration of N-acylated .alpha.-amino acids. These 5(4H)-oxazolones are readily substituted in the 4-position. Subsequent hydrolysis of 4,4-disubstituted-5(4H)-oxazolone ring results in .alpha.,.alpha.-disubstituted amino acids. However, it has not been previously known to substitute the ring system in an stereospecific fashion so as to generate enantiomerically enriched, .alpha.,.alpha.-disubstituted amino acids.